tbuckley/cabot-search huggingface dataset:
Presence of hyperdiploidy and history of tobacco use in African American patients with SMM.
Authors: Rujul H Parikh, Subir Goyal, Yuan Liu, Craig C. Hofmeister, Jonathan L. Kaufman, Leonard T. Heffner, Lawrence H Boise, Vikas Anand Gupta, Madhav V. Dhodapkar, Sagar Lonial, Ajay K. Nooka, Nisha S Joseph
Journal: Journal of Clinical Oncology (2023)

8062 Background: Smoldering multiple myeloma (SMM) has a clinically variable course in progression to active myeloma (MM). Accurate risk stratification is essential in identifying which patients may benefit from early therapeutic intervention. Current models do not account for the potential impact of race on risk of progression to SMM. Here, we seek to identify independent risk factors for progression in African American (AA) versus white patients in a real-world single institutional database of SMM patients. Methods: We retrospectively identified 224 patients (pts) with untreated SMM from 2007 to 2021 treated at our institution. Patient demographics and disease characteristics were obtained from our IRB-approved myeloma database. TTP was defined as the time from diagnosis of SMM to diagnosis of active MM, estimated by Kaplan-Meier and compared by log-rank test. Univariate analyses were performed using Cox proportional hazard models for TTP. Results: A total of 224 pts (AA 35%, white 47%, other/unknown 17%) were identified with median age 62y (range 32-82). Median follow-up was 4.3y in Whites and 5y in AA pts. Notable characteristics include M/F 45%/54%, IgG/IgA/FLC 76%/17%/6%, 30% current/past smoker (median 15 pack-years), 12% alcohol use (≥10 drinks/wk), 45% with BMI &gt; 30. Multiple cytogenetic abnormalities were defined as presence of ≥2 of the following: t(4;14), t(14;16), gain(1q21), del(1p), del(13), or del(17p). The median TTP (mTTP) was 6.8 [95% CI (3.7, 8.2)] years in whites and 5.6 [95% CI (4.6, 11.8)] years in AA. On univariate analysis, M-spike &gt; 1.5, involved K/L ratio &gt; 12, and bone marrow PC &gt; 20% were associated with increased risk of progression for both AA and whites (all p &lt; 0.05). As expected, gain of 1q21 was associated with increased risk of progression for both groups, though more pronounced in AA (HR 2.94, p = 0.025) versus whites (HR 2.33, p = 0.013). Hyperdiploidy was associated with shorter mTTP in AA (HR 3.03, p = 0.004) compared to whites (HR 1.39, p = 0.3). Multiple cytogenetic abnormalities was associated with shorter mTTP in whites (HR 2.63, p = 0.004) but was not statistically significant in AA (HR 2.63, p = 0.104). Interestingly, tobacco use was associated with shorter mTTP in Blacks (HR 2.94, p = 0.005) but not in whites (HR 0.96, p = 0.85). Conclusions: Understanding the potential impact of racial background on progression from SMM to MM is critical in the appropriate management of all patients with SMM. In this database, with a large proportion of AA patients, hyperdiploidy and +1q portend high risk of progression in AA patients. Further study is needed to better classify these potential differences to ensure risk stratification models are applicable to all patients.
Factors associated with utilization of palliative care among hospitalized patients with cholangiocarcinoma.
Authors: Gogo-Ogute Ibodeng, Inimfon Jackson, Geneva Guarin, Kannan Thanikachalam
Journal: Journal of Clinical Oncology (2023)

e24159 Background: Cholangiocarcinoma has a rising incidence and a low 5-year survival rate. Patients with this malignancy have a very high symptom burden, however, there are only a few studies reported on the prevalence of palliative care utilization in this population. This study examines the prevalence, sociodemographic, hospital-level, and patient-related factors associated with the utilization of palliative care among hospitalized patients with cholangiocarcinoma in the United States. Methods: Data from the National Inpatient Sample, 2016–2020, were used to conduct retrospective cohort analyses. Descriptive analyses were performed to evaluate the prevalence of palliative care consultations among hospitalized patients with a diagnosis of cholangiocarcinoma. Multivariable logistic regression models were used to examine the factors associated with the receipt of palliative care in this population. Results: Approximately 17.9% of our cohort received palliative care during their hospital stay. Cholangiocarcinoma patients aged 65 years and older were more likely to receive palliative care (AOR: 1.19; 95% CI: 1.06–1.32) compared to those less than 65 years. Female patients had 10% higher odds (95% CI: 1.02–1.18) of palliative care utilization relative to their male counterparts. Compared to patients on Medicare, those with Medicaid (AOR: 1.50; 95% CI: 1.29–1.75), private (AOR: 1.27; 95% CI: 1.13–1.42) or other insurance types (AOR: 2.31; 95% CI: 1.95–2.75) were more likely to receive palliative care during their hospital stay. While patients who had elective admissions were less likely (AOR: 0.45; 95% CI: 0.40–0.51) to utilize palliative care relative to those admitted non-electively, those admitted to urban teaching hospitals had 25% higher odds (AOR: 1.29; 95% CI: 1.06–1.57) of palliative care utilization when compared to patients admitted to rural hospitals. Additionally, hospitalized patients with a diagnosis of intrahepatic cholangiocarcinoma had 1.39 times higher odds (95% CI: 1.25–1.55) of receiving palliative care when compared to patients diagnosed with extrahepatic cholangiocarcinoma. Other factors associated with palliative care utilization were hospital region, Charlson comorbidity index and patient disposition. Conclusions: Palliative care consultations among hospitalized patients diagnosed with cholangiocarcinoma remain suboptimal. Our study highlights some of the sociodemographic and hospital-level barriers to the utilization of palliative care services which should guide healthcare providers on areas to improve upon with the goal of improving access to palliative care among hospitalized patients with cholangiocarcinoma.
Evaluation of prophylactic tocilizumab (toci) for the reduction of cytokine release syndrome (CRS) to inform the management of patients (pts) treated with teclistamab in MajesTEC-1.
Authors: Niels W.C.J. van de Donk, Alfred L. Garfall, Lotfi Benboubker, Katarina Uttervall, Kaz Groen, Laura Rosiñol, Caroline Hodin, Tara Stephenson, Danielle Trancucci, Alfredo Perales-Puchalt, Rachel Kobos, Arnob Banerjee, Maria-Victoria Mateos
Journal: Journal of Clinical Oncology (2023)

8033 Background: Teclistamab is the first BCMA × CD3 bispecific antibody approved for the treatment of relapsed/refractory multiple myeloma (RRMM). In MajesTEC-1, CRS occurred in 72.1% of pts treated at the recommended phase 2 dose (RP2D) of weekly teclistamab 1.5 mg/kg (50.3% grade [gr] 1; 21.2% gr 2; 0.6% gr 3), and was successfully managed using toci in 36.4% of pts (± other interventions) without affecting response to teclistamab. Emerging data show that prophylactic administration of toci prior to first dose of bispecific antibodies reduces CRS incidence and severity, which may facilitate outpatient initiation of therapy. The current analysis includes the first prospective study of effects of prophylactic toci on incidence and severity of CRS with teclistamab. Methods: Eligible pts were aged ≥18 y with RRMM and had previously received a PI, IMiD, and anti-CD38 antibody. Pts received subcutaneous teclistamab (following 2 step-up doses) in a prospective exploratory cohort at the RP2D or in a fixed-dose cohort. Toci (single 8 mg/kg IV dose) was given ≤4 hours before the first teclistamab step-up dose. CRS was graded per Lee et al 2014 and managed per institutional guidelines. Results: 14 pts were included: median age 64 y (range 50–82); all pts had ECOG score ≤1 and ISS I/II; 91% had standard cytogenetic risk; 21% had extramedullary plasmacytomas; 31% had ≥30% BMPCs; median 4 prior lines of therapy (range 2–7); 64% triple-class refractory. Median follow-up was 1.2 mo (range 0.2–4.6). CRS occurred in 4 pts (29%; no gr ≥3 CRS); 1 had a subsequent CRS event (table). Median time to onset was 2 d (range 1–3); median duration was 2 d (range 2–4); all events were managed with toci and resolved without teclistamab discontinuation. 7 of 14 pts had gr 3/4 neutropenia (consistent with the overall MajesTEC-1 population). 2/14 had a gr 3/4 infection. 2/14 had a neurotoxicity AE. Of the response evaluable patients, 4/7 responded. Cytokine and PK data in additional pts with longer follow-up will be presented to further inform pt management. Conclusions: A single dose of toci before teclistamab treatment appeared to reduce the incidence of CRS relative to the overall MajesTEC-1 study population with no new safety signals and no evidence of impact on response to teclistamab considering the short follow-up. Prophylactic toci has the potential to reduce CRS risk in pts with disease profiles suitable for outpatient dosing, reducing the burden of hospitalization during teclistamab step-up dosing. Clinical trial information: NCT03145181 , NCT04557098 . [Table: see text]
NGAL and KIM-1 as early biomarkers of cisplatin-associated nephrotoxicity.
Authors: Natalia Chebotareva, Lyudmila Zhukova, Tatyana Krasnova, Katerina Grechukhina
Journal: Journal of Clinical Oncology (2023)

e24080 Background: Cisplatin can cause renal injury in one-third of the patients. After the uptake by tubular renal cells cisplatin causes TNF-a immediate inflammation and death of tubular cell, ischemia and vascular damage on the kidney, which results in glomerular filtration rate (GFR) decrease (Toyuz et al, 2019). Serum creatinine is increased at the time of approximately 50% of nephrons are damaged. The identification of predictors and early markers of renal damage will make it possible to identify a high-risk group and monitor renal damage (Touyz, 2018). NGAL is activated immediately after ischemic or direct toxic damage to the kidneys in the distal segments of the nephron (Schmidt-Ott et al, 2007; Mishra). KIM-1 is an early marker of proximal tubule damage (Prasaja et al, 2015). Both NGAL and KIM-1 demonstrated their role of renal damage biomarkers in contrast-induced acute kidney injury. The goal of this study was to assess NGAL and KIM-1 as biomarkers of early nephrotoxicity induced by cisplatin and to assess their role as risk factors. Methods: The study included 50 patients who received cisplatin. Nephrotoxicity was determined as a decrease in GFR to &lt; 60 ml/min/1.73 m2 at 8 weeks from the initiation of therapy. The levels of KIM-1 and NGAL in urine samples were determined by ELISA before treatment and after 1, 2, 4 and 8 weeks of treatment. To assess risk factors for nephrotoxicity, a logistic regression analysis was performed with the inclusion of primary clinical and laboratory parameters. ROC-analysis was used to assess sensitivity and specificity of markers. Results: The decrease of GFR less then &lt; 60 ml/min/1.73 m2 at 8 weeks was observed in 11 (22%) of patients. There were no signs of increase of blood pressure in 8 weeks of observation. Serum creatinine increased clinically significant in 8 weeks after the start of therapy. The level of NGAL and KIM-1 rapidly increased in 1 week after the start of therapy (p &lt; 0.001) which is shown in Table. The unfavorable predictor of nephrotoxicity was a 1-week increase of urine NGAL and KIM-1: OR 8.37; 95%CI 4.64-95.84; p = 0.001. Both NGAL and KIM-1 demonstrated high sensitivity, specificity and area under the curve (AUC) – both 0.69 as early biomarkers of nephrotoxicity assessed after 8 weeks from the start of therapy. Conclusions: An increase of KIM-1 and NGAL observed earlier then serum creatinine increase. Elevation in 1 week after the initiation of therapy can predict nephrotoxicity with high specificity and sensitivity. At the same time an early increase in the concentrations of KIM-1 and in the urine is the independent risk factors for cisplatin-induced nephrotoxicity. [Table: see text]
Atypical new metastatic sites after immunotherapy in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M H&amp;NSCC).
Authors: John F. Deeken, Mahsa Ahmadi, Laura Johnston, David M. Heyer, Patty Lee, Katherine Niknia, Gopal Krishna Bajaj
Journal: Journal of Clinical Oncology (2023)

e18032 Background: Immunotherapy with PD-1 inhibitors (PD-1Is) nivolumab (N) or pembrolizumab (P) has led to significant improvements in overall survival in pts with R/M H&amp;NSCC. Common metastatic (met) sites for R/M H&amp;NSCC are locoregional in the H&amp;N area (LR), lung (L) and liver (LV). We investigated where patients developed met sites after successful treatment with PD-1Is. Methods: Eligible pts were treated with N or P for at least 3 months in the 1 st or 2 nd line setting and with at least stable disease as best response. Records were reviewed for initial sites of disease and whether metastatic sites developed after PD-1 therapies, including during subsequent lines of therapy. Patients could have more than one initial or progressive metastatic/recurrent sites of disease. Results: 26 eligible pts treated between 2016-2022 were identified with demographics as follows: 20 males/6 females; average age 65.3 yrs; primary diseases were 13 oropharynx (12 HPV+), 10 oral cavity, 1 larynx, and 2 nasopharynx; 8 received N and 18 got P (4 with chemotherapy); 22 were treated in 1 st line and 4 in 2 nd line. The median time on PD-1I therapy was 51.7 weeks (range 19 – 100). Best response was stable disease in 9 (35%), partial response in 15 (58%), and complete response in 2 (8%). Initial sites of disease were: LR 16 (62%), L 16 (62%), LV 2 (8%) and bone 2 (8%). In the 16 pts who developed new sites of disease, these included L in 5 (31%), LV in 4 (25%), bone in 7 (44%), abdomen/mesentery in 7 (44%), lower extremities in 4 (25%), and brain in 3 (19%). All 3 who developed CNS mets had HPV+ oropharynx cancer. Conclusions: Pts successfully treated with PD-1Is had uncommon sites of new metastatic disease, including in the lower extremities, abdomen, and brain. This has important ramifications for restaging scan requirements in these patients while on treatment. These results also raise the possibility of disease site sanctuaries resistant to immunotherapy, including in the abdomen, bone, and brain. Larger patient series should be investigated.
Association between body mass index and survival outcomes for patients with advanced non–small-cell lung cancer treated with immune checkpoint inhibitors: A systematic review and meta-analysis.
Authors: Yanxin Sun, Yuping Sun, Juan Li, Aiqin Gao
Journal: Journal of Clinical Oncology (2023)

e21136 Background: Growing researches have focused on obesity as an useful prognostic factor for pan-cancer patients with immmnotherapy. The role of body-mass index (BMI) in predicting response to ICIs is not consistent in different tumors. This meta-analysis was conducted to evaluate the relationship between BMI and outcome in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors, which is not clear as studies have demonstrated inconsistent results and significant interpretation biases. Methods: We searched PubMed and Embase, for relevant studies published up to December 2022. Title/abstract screening, full-text review, data extraction, and quality assessment were performed independently. Results: The correlation between BMI and prognosis in patients with advanced non-small cell lung cancer treated with ICIs was compared in ten trials encompassing 5000 individuals with the disease. The findings showedthat immunotherapy was significantly more effective for non-small cell lung cancer patients with a higher BMI compared to those with a lower BMI (OS: HR: 0.832, 95% CI: 0.725-0.955, p = 0.009; PFS: HR: 0.860, 95% CI: 0.771-0.960, p = 0.007). While，in the investigation of the obese group, no statistically significant differences were found. Conclusions: In patients with advanced non-small cell lung cancer treated with ICIs, appropriate higher BMI was significantly linked to better outcomes. However, discrepant findings from different cutoff subgroup analyses urgently call for further analysis.
Fellow-led didactics in a hematology/oncology fellowship program.
Authors: Rajat Thawani, Jeremy Paul Cetnar
Journal: Journal of Clinical Oncology (2023)

11026 Background: The pandemic in 2020 made us used to virtual learning, but as we recover from the pandemic, we are forced to rethink how we deliver education to trainees in medicine. The pandemic has led to a significantly decreased attention span and face to face interactions, in addition to an increased screen time. In our program, this led to us noting a lower engagement in the fellowship didactics as we recovered from the pandemic. This forced us to rethink how the Oregon Health &amp; Science University (OHSU) hematology and oncology fellowship delivers educational content. After interviewing all stakeholders, we moved to an in-person fellow led didactic approach, under the mentorship of a faculty expert who helps trainees design content and is present for discussion. The rationale behind this approach was to boost peer-to-peer learning, supply relevant content and increase engagement. The fellows and faculty were provided guidelines about length of talk, presentation of data and use of interactive tools. Methods: After 6 months of introducing fellow led didactics, we surveyed all fellows and select faculty who were mentors on more than one occasion about their opinion. A survey link was sent to all 12 fellows and 18 faculty members who regularly took part in fellowship didactics. Results: All 12 fellows responded to the survey. On a Likert scale of 1-5, they scored improvement in knowledge at 4.58 (0.64) and rated both the content and presenter at 4.25 (0.43). A third felt that this way of delivering didactics was a lot better and the rest felt it was a little better. On the negative side, they felt that they were spending more time preparing content (40% spent 7-9 hours a month) but were optimistic about lesser commitment next year as we bank the PowerPoint presentations. Nine of the 18 (50%) invited faculty responded to the survey, and on a scale of 1-5, they rated their improvement of knowledge as 4.44 (0.68). They scored the content and presenter at 4.44 (0.5) and 4.56 (0.68) respectively. 88.9% felt that the didactics were either a little or a lot better, and 11.1% felt them to be the same. On average, they spent less time on the content than they did if they were presenting. Conclusions: Overall, both faculty and fellows felt that this method of delivering didactics in a hematology oncology fellowship program was more effective. The fellows felt that they needed to put in extra hours for preparation, but this will probably go down as they build on earlier presentations.
Phase II study of durvalumab plus olaparib as maintenance therapy in extensive-stage small-cell lung cancer (TRIDENT): Preliminary efficacy and safety results.
Authors: Yan Huang, Jun Jia, Qiming Wang, Xianling Liu, Li Zhang
Journal: Journal of Clinical Oncology (2023)

8518 Background: First-line durvalumab in extensive-stage small-cell lung cancer (ES-SCLC) demonstrated significant improvement of OS in phase Ⅲ CASPIAN trial. PARP inhibitors have the potential to confer antitumor activity, modify tumor immunogenicity, and sensitize tumors to anti-PD-1/PD-L1 therapy. Durvalumab in combination with Olaparib (a PARPi) had clinical activity in relapsed SCLC in a phase Ⅰ/Ⅱ study. This phase Ⅱ study aimed to assess the efficacy and safety of durvalumab plus olaparib as maintenance therapy in patients with ES-SCLC. Methods: TRIDENT is a single arm, multicenter, phase Ⅱ study. Treatment-naive ES-SCLC aged ≥18 with ECOG PS 0-2 were eligible. Durvalumab (1500 mg) was concurrently administered with platinum–etoposide every 3 weeks for 4 cycles, followed by durvalumab 1500 mg every 4 weeks plus olaparib 300 mg twice daily until disease progression or unacceptable toxicity. The primary endpoint was the rate of progression free survival (PFS) at 12 months, the secondary endpoints included progression free survival, objective response rate (ORR) according to RECIST 1.1, duration of response (DoR), overall survival (OS) and safety profile. All patients should provide tumor sample for biomarker analysis (exploratory endpoint). Results: Between August 2021 and August 2022, 60 eligible patients were enrolled from 4 sites in China. At data cut-off (Jan 16 th , 2023), 18 (30%) patients were still on treatment. The median age was 63 years (range 57-68). The median cycle of durvalumab was 7 (range 1-17), and durvalumab plus olaparib as maintenance therapy was 3.5 (range 1-13). The PFS rate at 6-, 9-, 12-month were 49.7% [95%CI 37.8%-65.4%], 26.3% [95%CI 13.8%-40.3%] and 18% [95%CI 9.3%-34.7%], respectively. ORR was 75% (45/60), the median DoR was 5.0 months [95%CI 3.8-6.5]. With a median follow-up of 10.5 months, the median PFS was 5.8 months [95%CI 4.9-7.7] as calculated from the first cycle of durvalumab plus chemotherapy. The median OS was not reached [95%CI 10-NA]. Of all, treatment emergent adverse event (AE) occurred in 93.3% (56/60) patients, and AEs ≥ grade 3 occurred in 36.7% (22/60) patients. There were no unexpected adverse events identified in this study. There were 5 patients (8.3%) discontinued treatment and 1 death (1.6%) due to AE. Biomarker analysis is still on-going and will be presented in the meeting. Conclusions: TRIDENT is the first study to evaluate the efficacy and safety of durvalumab plus olaparib as maintenance therapy in Chinese ES-SCLC patients to date. The preliminary result warrant further investigation of this treatment modality in ES-SCLC. Clinical trial information: NCT05245994 .